Based upon newly discovered mechanisms to enhance circulation during CPR, the goal of this SBIR phase 1 application is to develop a comprehensive and novel non-invasive extracorporeal automated circulatory assist device to normalize blood flow during cardiac arrest and to provide adequate circulation for prolonged periods of time allowing for transport of patients to the hospital where they can receive more definite therapies. The device is designed to harness both the intrathoracic pump mechanism during CPR to provide sufficient forward flow, to refill the heart to maintain normal blood pressures, to lower intracranial pressures, and to further augment venous return and direct diastolic flow to the heart and brain by using synchronized lower extremity couterpulsation. The novel approach is also designed to reduce or eliminate the need for potentially harmful exogenous vasopressor therapies. To provide prolonged effective prolonged resuscitation, three core technologies will be combined into one device. They are: i) Active compression decompression (ACD) CPR with a pneumatic sternal compression device. ii) A means to provide intrathoracic pressure regulation coupled with a means to provide positive pressure ventilation. iii) Lower extremity counterpulsations (LECP) with a pneumatically driven shock-trousers-like device linked to the ACD CPR device. The LECP will be synchronized to inflate and compress the lower limbs during the decompression phase of the chest compression - decompression cycle. These 3 core technologies will be coordinated and controlled electronically to enhance cardiac preload, forward blood flow to the brain, and minimize intracranial resistance to cerebral perfusion. This unique combination of non-invasive mechanisms promises to provide a means to provide prolonged normal blood circulation until definitive care, such as coronary revascularization, can be provided in a controlled manner. The three specific aims of this research proposal are: 1) design and build a prototype non-invasive circulatory support device for the treatment of cardiac arrest to provide normal circulation to the heart and brain, 2) coordinate and test the different configurations of the CPR device system components in an animal model to maximize vital organ perfusion pressures and blood flow, and 3) demonstrate proof of concept that use of the novel CPR device will result in normal circulation for at least one hour of prolonged CPR, effective defibrillation, and 24-hour neurological-intact survival. Data from the sponsor's laboratory and from other laboratories have shown that prolonged CPR is feasible if circulation to the heart and brain during CPR and post-resuscitation care are optimized. The proposed device development and the proposed paradigm shift promises to provide a fundamental change in our understanding and ultimately clinical approach for the vast majority of patients, both young and old, who cannot be resuscitated with current basic and advanced life support techniques. PUBLIC HEALTH RELEVANCE: The goal of this SBIR phase 1 application is to further develop a comprehensive and novel extracorporeal circulatory assist device to normalize blood flow during cardiac arrest and to non- invasively provide adequate circulation for prolonged periods of time allowing for transport of patients to the hospital where they can receive more definite therapies. The device is designed to harness the intrathoracic pump mechanism during CPR to provide sufficient forward flow, to refill the heart to maintain normal blood pressures, and to lower intracranial pressures in the absence of exogenous vasopressor therapy. To provide prolonged effective prolonged resuscitation, three core technologies will be combined into one device. They are: i) Active compression decompression (ACD) CPR with a pneumatic sternal compression device. ii) A means to provide intrathoracic pressure regulation coupled with a means to provide positive pressure ventilation. iii) Lower extremity counterpulsations (LECP) with a pneumatically driven shock-trousers-like device linked to the ACD CPR device. The LECP will be synchronized to inflate and compress the lower limbs during the decompression phase of the chest compression - decompression cycle. These 3 core technologies will be coordinated and controlled electronically to enhance cardiac preload, forward blood flow to the brain, and minimize intracranial resistance to cerebral perfusion. This unique combination of non-invasive mechanisms promises to provide a means to provide prolonged normal blood circulation until definitive care, such as coronary revascularization, can be provided in a controlled manner. If this program is successful, the new resuscitation system has the potential to resuscitate approximately 50,000 more patients of the 400,000 sudden cardiac deaths that occur outside the hospital each year in the United States. This estimation does not take into account a nearly equal number of patients with sudden cardiac death that occur in-hospital each year.